The long-term objective of the proposed research is to develop and evaluate the use of real-time functional magnetic resonance imaging (rt-fMRI)-based neurofeedback signals as tools to study and modify the dynamics of reward anticipation and decision-making. The specific aims of the proposal are to investigate the use of rt-fMRI for revealing neural activation related to decision and reward-processing in real time, to test and optimize the efficacy of this real-time signal for neurofeedback-based voluntary modulation of neural activation in relevant brain regions, and to characterize the potential of such voluntary neuromodulation for modification of reward-evaluating and decision-making behavior. Adaptation of previously pioneered methods in rt-fMRI to the novel application of probing sub-cortical brain regions involved in the reward system will allow the exploration of this system and its interconnections in previously untenable ways, opening up previously hidden drives to conscious perception and perhaps permitting the exercise of voluntary intention on previously autonomous processes. Such explorations may shed light not only on the normal dynamic interactions between neural circuits of motivation and cognitive control, but also on the nature of particular dysfunctions jn those dynamics, which can lead to maladaptive behaviors and symptoms such as addiction and substance abuse. Voluntary modulation of activation in these circuits might then be utilized for the purpose of modifying maladaptive behavior. Specific methodologies for pursuing these goals include optimization of scanning, signal-processing, and neurofeedback protocol parameters; basic mapping of human capacity for voluntary neuromodulation in the reward system and factors influencing this capacity; and standard statistical testing of behavioral effects following neurofeedback-based voluntary interventions in neural activation. Expected behavioral effects include modulation of risk-sensitivity and cue-elicited craving. Beyond the basic science appeal of new insight into the dynamic interplay of cognitive and affective neural systems, findings revealed in the proposed research may lead to new and effective forms of noninvasive therapeutic intervention, achieved by the voluntary effort of the patient, in order to reprogram reward circuitry in the brain. Areas of particular relevance to this approach would be disorders affecting the brain's mesolimbic pathway, such as addiction, depression, and attention-deficit/hyperactivity disorder. [unreadable] [unreadable] [unreadable]